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https://www.readbyqxmd.com/read/28944844/h2o2-induces-caveolin%C3%A2-1-degradation-and-impaired-mitochondrial-function-in-e11-podocytes
#1
Ya-Hui Chen, Wei-Wen Lin, Chin-San Liu, Shih-Li Su
Increased intercellular reactive oxygen species (ROS) levels are the major cause of podocyte injury with proteinuria. Caveolin‑1 (CAV‑1) is an essential protein component of caveolae. CAV‑1 participates in signal transduction and endocytic trafficking. Recent research has indicated that CAV‑1 regulates oxidative stress‑induced pathways. The present study used hydrogen peroxide (H2O2) at nontoxic concentrations to elevate the level of ROS in E11 podocytes. Treatment with 500 and 1,000 µM H2O2 for 1 h significantly reduced CAV‑1 expression levels...
September 18, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28944838/effect-of-antioxidant-of-bamboo-leaves-on-gene-expression-associated-with-mouse-embryonic-fibroblast-reproduction-and-embryonic-development
#2
Feng Yu, Xiaowei Qian, Zhanghui Zeng, Xiaoli Zhao, Rong Hou, Zhihe Zhang, Hongwu Bian, Ning Han, Junhui Wang, Muyuan Zhu
Antioxidant of bamboo leaves (AOB) was certified to be a natural antioxidant by the Chinese Ministry of Health in 2003. However, the effects of AOB on animal reproductive and developmental functions remain unclear. The present study aimed to investigate the effects of different concentrations of AOB on mouse embryonic fibroblast (MEF) cells, and to examine the underlying molecular mechanism through which AOB affects the proliferation and apoptosis of MEFs. MEFs prepared from individual embryos were treated with various dosages of AOB...
September 18, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28944608/coexistence-of-mutations-in-keratin-10-krt10-and-the-mitochondrial-genome-in-a-patient-with-ichthyosis-with-confetti-and-leber-s-hereditary-optic-neuropathy
#3
Agnieszka Kalinska-Bienias, Agnieszka Pollak, Cezary Kowalewski, Urszula Lechowicz, Piotr Stawinski, Aleksandra Gergont, Joanna Kosinska, Ewa Pronicka, Pawel Kowalski, Katarzyna Wozniak, Rafal Ploski
Ichthyosis with confetti (IWC) is a severe congenital genodermatosis characterized by ichthyosiform erythroderma since birth and confetti-like spots of normal skin appearing in childhood as a results of revertant mosaicism. This disorder is caused by mutations in KRT10 or KRT1 genes. We report a 16-year-old boy who presented ichthyosiform erythroderma with severe desquamation since birth and gradually worsening psycho-neurological symptoms (mental retardation, ataxia, dystonia, hypoacusis). The patient conspicuously lacked typical confetti-like spots at the age of 16...
September 25, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28944344/irf4-couples-anabolic-metabolism-to-th1-cell-fate-determination
#4
Radomir Kratchmarov, Simone A Nish, Wen-Hsuan W Lin, William C Adams, Yen-Hua Chen, Bonnie Yen, Nyanza J Rothman, Ulf Klein, Steven L Reiner
Anabolic metabolism in lymphocytes promotes plasmablast and cytotoxic T cell differentiation at the expense of self-renewal. Heightened expression and function of the transcription factor IFN regulatory factor 4 (IRF4) accompany enhanced anabolic induction and full commitment to functional differentiation in B cells and CD8(+) T cells. In this study, we used a genetic approach to determine whether IRF4 plays an analogous role in Th1 cell induction. Our findings indicate that IRF4 promotes determined Th1 cell differentiation in tandem with anabolic metabolism of CD4(+) T cells...
September 1, 2017: Immunohorizons
https://www.readbyqxmd.com/read/28944303/resveratrol-and-exercise-to-treat-functional-limitations-in-late-life-design-of-a-randomized-controlled-trial
#5
Andrew S Layne, Lisa M Krehbiel, Robert T Mankowski, Stephen D Anton, Christiaan Leeuwenburgh, Marco Pahor, Bhanuprasad Sandesara, Samuel S Wu, Thomas W Buford
Skeletal muscle mitochondrial function declines with age and is a key factor in the maintenance of physical function among older adults. Research studies from animals and humans have consistently demonstrated that exercise improves skeletal muscle mitochondrial function in early and middle adulthood. However, mitochondrial adaptations to both acute and chronic exercise are attenuated in late life. Thus, there is an important need to identify adjuvant therapies capable of augmenting mitochondrial adaptations to exercise (e...
June 2017: Contemporary Clinical Trials Communications
https://www.readbyqxmd.com/read/28944215/endoplasmic-reticulum-mitochondria-calcium-communication-and-the-regulation-of-mitochondrial-metabolism-in-cancer-a-novel-potential-target
#6
REVIEW
Galdo Bustos, Pablo Cruz, Alenka Lovy, César Cárdenas
Cancer is characterized by an uncontrolled cell proliferation rate even under low nutrient availability, which is sustained by a metabolic reprograming now recognized as a hallmark of cancer. Warburg was the first to establish the relationship between cancer and mitochondria; however, he interpreted enhanced aerobic glycolysis as mitochondrial dysfunction. Today it is accepted that many cancer cell types need fully functional mitochondria to maintain their homeostasis. Calcium (Ca(2+))-a key regulator of several cellular processes-has proven to be essential for mitochondrial metabolism...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28943954/epigallocatechin-3-gallate-suppresses-cell-proliferation-and-promotes-apoptosis-in-ec9706-and-eca109-esophageal-carcinoma-cells
#7
Liang Liu, Jing Zuo, Guangda Wang
Epigallocatechin-3-gallate (EGCG) is a component of green tea with anticancer effects that have been demonstrated in multiple types of cancer, but few reports exist concerning its effect in esophageal squamous cell carcinoma cells. The present study investigated apoptosis induced by EGCG treatment and the underlying molecular mechanisms in Eca109 and Ec9706 human esophageal squamous cell carcinoma cells. The apoptosis rate following treatment with various concentration of EGCG for 24 h was detected by flow cytometry...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28943437/inhibiting-prenylation-augments-chemotherapy-efficacy-in-renal-cell-carcinoma-through-dual-inhibition-on-mitochondrial-respiration-and-glycolysis
#8
Jiangrong Huang, Xiaoyu Yang, Xiaochun Peng, Wei Huang
Prenylation is a posttranslational lipid modification required for the proper functions of a number of proteins involved in cell regulation. Here, we show that prenylation inhibition is important for renal cell carcinoma (RCC) growth, survival and response to chemotherapy, and its underlying mechanism may be contributed to mitochondrial dysfunction. We first demonstrated that a HMG-CoA reductase inhibitor pitavastatin inhibited mevalonate pathway and thereby prenylation in RCC cells. In addition, pitavastatin is effective in inhibiting growth and inducing apoptosis in a panel of RCC cell lines...
September 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28943303/human-mmaa-induces-the-release-of-inactive-cofactor-and-restores-methylmalonyl-coa-mutase-activity-through-their-complex-formation
#9
Toshiko Takahashi-Iñiguez, Alfonso González-Noriega, Colette Michalak, María Elena Flores
Human mitochondrial methylmalonyl-CoA mutase (hMCM) is an isomerase that converts methylmalonyl-CoA to succinyl-CoA, a crucial step for the incorporation of some compounds derived from the diet into the central metabolism. hMCM employs highly reactive radicals from its cofactor (adenosylcobalamin, AdoCbl) to perform its reaction. Our previous work demonstrated that hMCM loses activity during catalysis and that the interaction with human MMAA (hMMAA), a GTPase protein, avoided this loss or restored hMCM activity...
September 21, 2017: Biochimie
https://www.readbyqxmd.com/read/28943275/mifepristone-enhances-insulin-stimulated-akt-phosphorylation-and-glucose-uptake-in-skeletal-muscle-cells
#10
Izela Bernal-Sore, Mario Navarro-Marquez, César Osorio-Fuentealba, Francisco Díaz-Castro, Andrea Del Campo, Camila Donoso-Barraza, Omar Porras, Sergio Lavandero, Rodrigo Troncoso
Mifepristone is the only FDA-approved drug for glycaemia control in patients with Cushing's syndrome and type 2 diabetes. Mifepristone also has beneficial effects in animal models of diabetes and patients with antipsychotic treatment-induced obesity. However, the mechanisms through which Mifepristone produces its beneficial effects are not completely elucidated. PURPOSE: To determine the effects of mifepristone on insulin-stimulated glucose uptake on a model of L6 rat-derived skeletal muscle cells...
September 21, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28943271/transmembrane-%C3%AE-barrels-evolution-folding-and-energetics
#11
REVIEW
Deepti Chaturvedi, Radhakrishnan Mahalakshmi
The biogenesis of transmembrane β-barrels (outer membrane proteins, or OMPs) is an elaborate multistep orchestration of the nascent polypeptide with translocases, barrel assembly machinery, and helper chaperone proteins. Several theories exist that describe the mechanism of chaperone-assisted OMP assembly in vivo and unassisted (spontaneous) folding in vitro. Structurally, OMPs of bacterial origin possess even-numbered strands, while mitochondrial β-barrels are even- and odd-stranded. Several underlying similarities between prokaryotic and eukaryotic β-barrels and their folding machinery are known; yet, the link in their evolutionary origin is unclear...
September 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28943110/therapies-for-mitochondrial-diseases-and-current-clinical-trials
#12
REVIEW
Ayman W El-Hattab, Ana Maria Zarante, Mohammed Almannai, Fernando Scaglia
Mitochondrial diseases are a clinically and genetically heterogeneous group of disorders that result from dysfunction of the mitochondrial oxidative phosphorylation due to molecular defects in genes encoding mitochondrial proteins. Despite the advances in molecular and biochemical methodologies leading to better understanding of the etiology and mechanism of these diseases, there are still no satisfactory therapies available for mitochondrial disorders. Treatment for mitochondrial diseases remains largely symptomatic and does not significantly alter the course of the disease...
September 18, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28943100/validation-of-a-pharmacological-model-for-mitochondrial-dysfunction-in-healthy-subjects-using-simvastatin-a-randomized-placebo-controlled-proof-of-pharmacology-study
#13
Marcus P J van Diemen, Cécile L Berends, Naila Akram, Joep Wezel, Wouter M Teeuwisse, Bert G Mik, Hermien E Kan, Andrew Webb, Jan Willem M Beenakker, Geert Jan Groeneveld
Proof-of-pharmacology models to study compounds in healthy subjects offer multiple advantages. Simvastatin is known to induce mitochondrial dysfunction at least partly by depletion of co-enzyme Q10. The goal of this study was to evaluate a model of simvastatin-induced mitochondrial dysfunction in healthy subjects and to determine whether mitochondrial dysfunction could be pharmacologically reversed by treatment with co-enzyme Q10 (ubiquinol). Subjects received simvastatin 40mg/day for 8 weeks. After 4 weeks, subjects were randomized to receive ubiquinol 300mg/day or placebo in a double-blinded fashion...
September 21, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28942965/biallelic-c1qbp-mutations-cause-severe-neonatal-childhood-or-later-onset-cardiomyopathy-associated-with-combined-respiratory-chain-deficiencies
#14
René G Feichtinger, Monika Oláhová, Yoshihito Kishita, Caterina Garone, Laura S Kremer, Mikako Yagi, Takeshi Uchiumi, Alexis A Jourdain, Kyle Thompson, Aaron R D'Souza, Robert Kopajtich, Charlotte L Alston, Johannes Koch, Wolfgang Sperl, Elisa Mastantuono, Tim M Strom, Saskia B Wortmann, Thomas Meitinger, Germaine Pierre, Patrick F Chinnery, Zofia M Chrzanowska-Lightowlers, Robert N Lightowlers, Salvatore DiMauro, Sarah E Calvo, Vamsi K Mootha, Maurizio Moggio, Monica Sciacco, Giacomo P Comi, Dario Ronchi, Kei Murayama, Akira Ohtake, Pedro Rebelo-Guiomar, Masakazu Kohda, Dongchon Kang, Johannes A Mayr, Robert W Taylor, Yasushi Okazaki, Michal Minczuk, Holger Prokisch
Complement component 1 Q subcomponent-binding protein (C1QBP; also known as p32) is a multi-compartmental protein whose precise function remains unknown. It is an evolutionary conserved multifunctional protein localized primarily in the mitochondrial matrix and has roles in inflammation and infection processes, mitochondrial ribosome biogenesis, and regulation of apoptosis and nuclear transcription. It has an N-terminal mitochondrial targeting peptide that is proteolytically processed after import into the mitochondrial matrix, where it forms a homotrimeric complex organized in a doughnut-shaped structure...
September 19, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28942964/fine-mapping-and-functional-analysis-reveal-a-role-of-slc22a1-in-acylcarnitine-transport
#15
Hye In Kim, Johannes Raffler, Wenyun Lu, Jung-Jin Lee, Deepti Abbey, Danish Saleheen, Joshua D Rabinowitz, Michael J Bennett, Nicholas J Hand, Christopher Brown, Daniel J Rader
Genome-wide association studies have identified a signal at the SLC22A1 locus for serum acylcarnitines, intermediate metabolites of mitochondrial oxidation whose plasma levels associate with metabolic diseases. Here, we refined the association signal, performed conditional analyses, and examined the linkage structure to find coding variants of SLC22A1 that mediate independent association signals at the locus. We also employed allele-specific expression analysis to find potential regulatory variants of SLC22A1 and demonstrated the effect of one variant on the splicing of SLC22A1...
September 14, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28942795/genetics-of-mitochondrial-disease
#16
Russell P Saneto
Mitochondria are intracellular organelles responsible for adenosine triphosphate production. The strict control of intracellular energy needs require proper mitochondrial functioning. The mitochondria are under dual controls of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). Mitochondrial dysfunction can arise from changes in either mtDNA or nDNA genes regulating function. There are an estimated ∼1500 proteins in the mitoproteome, whereas the mtDNA genome has 37 proteins. There are, to date, ∼275 genes shown to give rise to disease...
2017: Advances in Genetics
https://www.readbyqxmd.com/read/28942573/berberine-inhibits-oxygen-consumption-rate-independent-of-alteration-in-cardiolipin-levels-in-h9c2-cells
#17
Wenguang Chang, Ming Zhang, Li Chen, Grant M Hatch
Small clinical studies have shown that oral treatment with the plant alkaloid berberine (BBR) reduces blood glucose levels similar to that of metformin and have promoted its use as a novel anti-diabetic therapy. However, in vitro studies have shown that high concentrations of BBR potently inhibit cell proliferation through inhibition of mitochondrial function. Cardiolipin (Ptd2Gro) is a key phospholipid required for regulating mitochondrial bioenergetic function. We examined if BBR inhibited oxygen consumption rate in H9c2 cardiac myocytes through alteration in Ptd2Gro metabolism...
September 23, 2017: Lipids
https://www.readbyqxmd.com/read/28942427/binding-of-fundc1-with-inositol-1-4-5-trisphosphate-receptor-in-mitochondria-associated-endoplasmic-reticulum-er-membranes-maintains-mitochondrial-dynamics-and-function-in-hearts-in-vivo
#18
Shengnan Wu, Qiulun Lu, Qilong Wang, Ye Ding, Zejun Ma, Xiaoxiang Mao, Kai Huang, Zhonglin Xie, Ming-Hui Zou
Background -FUN14 domain containing 1 (FUNDC1) is a highly conserved outer mitochondrial membrane protein. The aim of this study is to examine if FUNDC1 modulates the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), mitochondrial morphology, and function in cardiomyocytes and in intact hearts. Methods -The impacts of FUNDC1 on MAMs formation and cardiac functions were studied in mouse neonatal cardiomyocytes, in mice with cardiomyocyte-specific Fundc1 gene knockout (Fundc1(f/Y)/Cre(αMyHC+/-) ), and in the cardiac tissues of the patients with heart failure...
September 23, 2017: Circulation
https://www.readbyqxmd.com/read/28942281/antihypertrophic-effects-of-small-molecules-that-maintain-mitochondrial-atp-levels-under-hypoxia
#19
Hiroaki Nagai, Tomoko Satomi, Akiko Abiru, Kazumasa Miyamoto, Koji Nagasawa, Minoru Maruyama, Satoshi Yamamoto, Kuniko Kikuchi, Hiromitsu Fuse, Masakuni Noda, Yoshiyuki Tsujihata
Since impaired mitochondrial ATP production in cardiomyocytes is thought to lead to heart failure, a drug that protects mitochondria and improves ATP production under disease conditions would be an attractive treatment option. In this study, we identified small-molecule drugs, including the anti-parasitic agent, ivermectin, that maintain mitochondrial ATP levels under hypoxia in cardiomyocytes. Mechanistically, transcriptomic analysis and gene silencing experiments revealed that ivermectin increased mitochondrial ATP production by inducing Cox6a2, a subunit of the mitochondrial respiratory chain...
September 19, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28942082/elucidation-of-protective-efficacy-of-pentahydroxy-flavone-isolated-from-madhuca-indica-against-arsenite-induced-cardiomyopathy-role-of-nrf-2-ppar-%C3%AE-c-fos-and-c-jun
#20
Anwesha A Mukherjee, Amit D Kandhare, Subhash L Bodhankar
BACKGROUND: Madhuca indica J. F. Gmel. (Sapotaceae) is widely used ethnobotanically as anti-diabetic, antipyretic, hepatoprotective, anti-inflammatory and analgesic. It was shown to possess potent anti-apoptotic property. THE AIM OF THE STUDY: To evaluate the possible mechanism of action of isolated phytoconstituent from Madhuca indica Leaves methanolic extract (MI-ALC) on arsenic-induced cardiotoxicity in rats. MATERIALS AND METHODS: The 3,5,7,3',4'-Pentahydroxy flavone (QTN) was isolated and characterized by using HPTLC, (1)H NMR, and LC-MS from MI-ALC...
September 1, 2017: Environmental Toxicology and Pharmacology
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